The rule of thumb I've heard is that you need 10mm of clearance between your tire and the fender, but I believe that's intended to prevent sticks jamming the wheel. This will depend somewhat on your frame, I think.

Width is really about how wide the fender needs to be to block spray from the tire. I would guess that as long as the fender is wider than the tire it will help, but if it's not a lot wider it won't catch everything.

I've got all three sizes of Cascadias, though I haven't actually used the 45mm set yet. I have laid it on a set of 700x40 Conti TownRides to eye it up, and I think I'd be willing to try that. The 29ers are really wide, and they barely fit between the seat stays on my Marin Muirwoods 29er. If your bike isn't a 29er, I wouldn't expect them to fit without modification. I also have a set of SKS P50's that were supposed to work with either 700c or 26" wheels, but they didn't come down far enough in the rear (with the aforementioned Contis) to keep my back clean.

It's probably worth noting that the 29er Cascadias have longer V-stays than the hybrid/touring version. If you find that this is a problem, you can order the longer stays directly from Planet Bike for a very reasonable cost.

If I were in your position, I'd try the 45mm Cascadias and maybe consider a slightly narrower tire sometime down the road.